The goal of this competing continuation request is to examine the role of genetic and family environmental influences, and their interaction, in the development and course of alcohol use disorders (AUD). This is to be achieved using a research strategy that incorporates 3 novel features: (a) use of the infrequently implemented yet powerful children of twins (COT) design involving twins who are concordant or discordant for-AUD as well as control pairs; (b) assessment of children of alcoholic mothers; (c) use of a prospective design which allows for the description of offspring development from preadolescence through the late twenties. The COT design is particularly well suited for studying environmental variables associated with maternal alcoholism in that statistical controls for genetic influences are embedded within the design, providing the opportunity to isolate environmental variables that are etiologically relevant to the development of alcohol problems. It is also well suited for detecting the contribution of genetic transmission to the association between AUDs in parents, and other disorders in offspring (e.g. Attention Deficit Hyperactivity Disorder, ADHD), as well as potential genotype x environment interaction effects. The assessment of twin mothers will fill an important research need in the field and will allow for comparisons with our MARC-affiliated studies involving the same design but based on twin fathers. Finally, our longitudinal, prospective design will allow us to make much stronger statements concerning the development of AUD than would be possible using only retrospective data from a cross-sectional study. During the renewal period, we will continue to expand our recruitment efforts, broadening our eligibility criteria to include mothers with offspring as young as 7 years. In so doing we will be able to confirm or disconfirm our emerging data based on retrospective reports of twin mothers about their adolescent and young adult offspring on disorders with early childhood onset (ADHD, Oppositional Defiant Disorder [ODD], conduct disorder [CD]). We will continue follow-up assessments by maternal interview (offspring aged 9-18) and offspring interview (aged 11-30). By the end of the renewal period, samples will be sufficiently large so that complex cross-sectional and longitudinal analyses will be firmly based.